Abstract
Mesenchymal stem/progenitor cells (MSCs) are key players in regenerative medicine, relying principally on their differentiation/regeneration potential, immunomodulatory properties, paracrine effects, and potent homing ability with minimal if any ethical concerns. Even though multiple preclinical and clinical studies have demonstrated remarkable properties for MSCs, the clinical applicability of MSC-based therapies is still questionable. Several challenges exist that critically hinder a successful clinical translation of MSC-based therapies, including but not limited to heterogeneity of their populations, variability in their quality and quantity, donor-related factors, discrepancies in protocols for isolation, in vitro expansion and premodification, and variability in methods of cell delivery, dosing, and cell homing. Alterations of MSC viability, proliferation, properties, and/or function are also affected by various drugs and chemicals. Moreover, significant safety concerns exist due to possible teratogenic/neoplastic potential and transmission of infectious diseases. Through the current review, we aim to highlight the major challenges facing MSCs' human clinical translation and shed light on the undergoing strategies to overcome them.
Highlights
Tissue engineering combines stem/progenitor cells with proper signaling molecules to be seeded on biocompatible scaffolds in the presence of physical stimuli to function in place of or to support regeneration of specific tissues or organs [1,2,3]
Further limitations include the probability for cell contamination during sorting procedures, physical stresses exerted on the cells [208], and the dependence on adherent cell purification, where the use of enzymes for cell detachment can cause proteolytic damage to cell surface proteins [61]
Some of those concerns were postulated to be overcome with the development of the CliniMACS Cell Isolation System, a device that is currently clinically approved and takes advantage of conjugating colloidal suspension of superparamagnetic microbeads to a monoclonal anti-human antibody that is capable of binding to its antigen in bone marrow, umbilical cord blood products, and peripheral blood in a sterile good manufacturing practice (GMP) system [209]
Summary
Tissue engineering combines stem/progenitor cells with proper signaling molecules to be seeded on biocompatible scaffolds in the presence of physical stimuli to function in place of or to support regeneration of specific tissues or organs [1,2,3]. Mesenchymal stem/progenitor cells (MSCs) are key players in regenerative medicine, owing to their remarkable differentiation and regeneration potentials in addition to their immunomodulatory properties, paracrine effect [4, 5], and potent homing ability with no ethical concerns [6,7,8]. MSCs are multipotent cells, hallmarked by their ability to differentiate into a variety of cell types upon stimulation. They should at least express clusters of differentiation (CD) CD105, CD90, and CD73 and lack the expression of CD11b, CD79a, CD19, and human leukocyte antigen-DR isotype (HLA-DR) [9]. We aim to highlight the major obstacles facing MSCs’ human clinical translation and how they can be overcome
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